Growth of tissue in both normal and disease depends on the balance between cellular proliferation and programmed cell death (apoptosis). Decision to cell hormones, calcium balance, ATP, p53, Bcl-2 family and others. Calcium has been known to be a key regulator of cellular proliferation. Previously, it has been shown that high calcium concentration (20-50 mM) completely degrades important proteins like Hsp70, calcineurin, calmodulin, ubiquitin, casein and m-calpain in vitro (Sen 1996). The ability of calcium to degrade proteins depends on PESTDY sequence. For this reason, it could be hypothesized that calcium in combination with anti-angiogenic agents, electron transport chain inhibitors, and neoplastic agents would induce apoptosis more efficiently at a lower concentration than without calcium. Specific biochemical markers for apoptosis such as DNA fragmentation, cytochrome c release, CPP32/caspase-3, PARP, Bcl-2, Bax and p53 expression have been selected to measure the effectiveness of chemical agents to induce apoptosis in cultured human breast cancer cells (MCF-7 & BT-20). The cells will be exposed to various concentrations of calcium chloride (1-5 nM) in combination with rotenone (10nM-10muM), thalidomide (10nM- 10muM), methotrexate (10nM-10muM), 2-methoxyestradiol (10 nM- 10muM) and buthionine sulfoximine (10 nM-10muM) to see how effectively it induces apoptosis. Since calcium is one of the triggers for apoptosis and when combined with other apoptotic agents will show greater additive effect at a much lower dose than when treated with a single agent or in combination with other agents without calcium. Exploitation of cell's inherent apoptotic apoptotic mechanism would be a better therapeutic alternative for cancer. This study will provide a better understanding of calcium's potential as a therapeutic agent in the war against cancer.